Slides on drug-eluting stents

1. A Pooled Analysis of 38 Trials Comparing Drug-Eluting Stents and Bare-Metal Stents Funding and Validation of Statistical Models The Swiss National Science Foundation Stettler C., et al., Lancet 2007;370:937-48. Outcomes Associated with Drug-Eluting and Bare-Metal Stents: A Collaborative Network Meta-Analysis

7. Identification of Eligible Randomized Trials 870 potentially eligible reports identified and screened for retrieval 786 reports excluded: 424 with different interventions 254 reviews or pooled analyses 98 observational studies 10 case reports 84 reports retrieved for detailed evaluation (41 trials) 6 reports excluded (3 trials): 2 (1 trial) with different interventions 4 (2 trials) subgroup analyses 78 reports included (38 trials with 40 comparisons): 7 PES vs. BMS 16 SES vs. BMS 14 PES vs. SES 1 PES vs. SES vs. BMS Stettler C., et al., Lancet 2007;370:937-48.

8. 16 SES vs. BMS Trials Included * Cardiac death ** Vessel-related death SES vs. BMS Study N Primary Endpoint Lesion Length (mm) RVD (mm) # of Sites Stettler C., et al., Lancet 2007;370:937-48. 1 NA  28 Late Lumen Loss 104 Ortolani et al. 1 NA NA Late Lumen Loss 308 MISSION 1 2.5-4.0  66 Late Lumen Loss 75 RRISC 16 2.5-3.5  42 Late Lumen Loss 200 SCORPIUS NA NA NA Late Lumen Loss 83 DECODE 1 NR NR Binary Restenosis 320 SESAMI 48 2.25-3.5  30 VRD**, AMI, TVR 715 TYPHOON 4 2.25-4.5  15* Min Lumen Diam 322 SCANDSTENT 2 NR NR Binary Restonsis 200 PRISON II 2 NR NR Binary Restenosis 500 Pache et al 4 < 4.0 NR Late Lumen Loss 160 DIABETES 20 < 2.75  33 Binary Restenosis 257 SES-SMART 8 2.5-3.0 15-32 Min Lumen Diam 100 C-SIRIUS 35 2.5-3.0 15-32 Min Lumen Diam 352 E-SIRIUS 53 2.5-3.5 15-30 CD*, AMI, TVR 1,058 SIRIUS 19 2.5-3.5  18 Late Lumen Loss 238 RAVEL

9. 7 PES vs. BMS Trials Included PES vs. BMS Study N Primary Endpoint Lesion Length (mm) RVD (mm) # of Sites Stettler C., et al., Lancet 2007;370:937-48. 1 NA NA NA 164 HAAMU-STENT 2 > 2.5 NR Cardiac Death, AMI, TLR 619 PASSION 44 2.5-3.75 18-40 TVR 446 TAXUS VI 66 2.25-4.0 10-46 TVR 1172 TAXUS V 73 2.5-3.75 10-28 TVR 1314 TAXUS IV 38 3.0-3.5  12 Neointimal Proliferation 536 TAXUS II 3 3.0-3.5  12 Death, AMI, TVR, ST 61 TAXUS I

10. 15 SES vs. PES Trials Included SES vs. PES Study N Primary Endpoint Lesion Length (mm) RVD (mm) # of Sites SES vs. PES vs. BMS Study N Primary Endpoint Lesion Length (mm) RVD (mm) # of Sites Stettler C., et al., Lancet 2007;370:937-48. NA NA NA NA 416 Han et al. 1 2.5-3.7  16 NIH 100 Petronio et al. 1 < 2.5 > 20 NIH 70 Cervinka et al. 5 NA NA Cardiac Death, AMI, TLR, TVR, TVF 2098 SORT OUT II NA NA NA Late Lumen Loss 231 PROSIT 5  2.5  25 Binary Restenosis 500 LONG DES II 1 2.5-3.5 NA Death, AMI, TVR 449 Zhang et al 2 < 2.8 NR Late Lumen Loss 360 ISAR-SMART-3 90 2.25-3.0 > 15 Binary Restenosis 1353 REALITY 2 < 2.5 < 20 Binary Restenosis 652 CORPAL 2 2.25-4.0 NR MACE 1012 SIRTAX 2 NR NR Late lumen Loss 250 ISAR-DIABETES 2 NR NR Binary Restenosis 200 ISAR-DESIRE 1 NR NR Death, AMI, TLR, ST 202 TAXi 1  4 NR Cardiac Death, MI, TVR 826 BASKET

11. Key Baseline Predictors of Restenosis in Complex DES vs. BMS Trials* Study Les. Length (mm) RVD (mm) DM (%) * Excludes RCTs enrolling simple/moderate patients/lesions: RAVEL, SIRIUS trials, Pache, and Ortolani, TAXUS II, and TAXUS IV ** Occlusion length † SCANDSTENT enrolled patients with occluded, bifurcational, ostial, or angulated lesions; TAXUS V focused enrollment to include patients with longer lesions and patients requiring either 2.25 or 4.0 mm stents. TAXUS VI focused on enrolling patients with longer lesions. Type Stent Length (mm) n Pt / Vessel Type Citations: 1. JAMA 2004;292:2727-34 2. Circulation 2006;114:921-28 3. JACC 2006;48:2423-31 4. Am J Cardiol 2005;96(7A):31H 5. Annual Transcatheter Cardiovascular Therapeutics meeting Oct 22-27, 2006 Abstract 288 6. Circulation 2005;112:2175-83 7. JACC 2006;47:449-55 8. JAMA 2005;294:1215-23 9. Circulation 2005;112:3306-13 10. NEJM 2006;355:1093-104 11. JACC 2007;49:1924-30 12. Annual AHA meeting Nov 12-15, 2006 13. NEJM 2006;355: 1105-13 14. Annual Transcatheter Cardiovascular Therapeutics meeting Oct 22-27, 2006 Abstract 178 HAAMU-STENT 14 PASSION 13 MISSION 12 SESAMI 11 TYPHOON 10 TAXUS VI 9 TAXUS V 8 SCANDSTENT 7 DIABETES 6 SCORPIUS 5 DECODE 4 RRISC 3 PRISON II 2 SES-SMART 1 AMI High-Risk † DM SVG CTO RVD  2.75 2.86 ± 0.53 26 18.8 ± 13.0 18 322 SES 2.33 ± 0.6 NA 14.6 ± 8 100 160 SES 2.78 ± 0.50 22.1 ± 8.6 NA 16 715 SES 2.81 ± 0.48 33.7 ± 10.79 20.94 ± 7.21 20 446 PES 19.0 ± 5.6 26.5 ± 12.8 16.9 ± 4.1 28.7 ± 13.2 19.6 ± 9.0 20.9 ± 8.45 23.4 ± 7.0 31.9 ± 15.3 16.99 ± 5.71 Not reported 15 164 PES 3.13 ± 0.43 NA 11 619 PES 2.75 ± 0.54 NA NA 308 SES 21 32 100 100 15 13 25 NA NA 320 SES 2.68 ± 0.58 17.3 ± 9.0 1172 PES 2.54 ± 0.45 11.2 ± 4.6 200 SES 2.51 ± 0.35 15.06 ± 6.34 83 SES 2.38 ± 0.57 NA 75 SES 2.53 ± 0.67 16.0 ± 9.3** 200 SES 2.22 ± 0.29 13.01 ± 6.53 257 SES

17. Cumulative Incidence of All Death Stettler C., et al., Lancet 2007;370:937-48.

18. Cumulative Incidence of Cardiac Death Stettler C., et al., Lancet 2007;370:937-48.

19. Cumulative Incidence of Myocardial Infarction Stettler C., et al., Lancet 2007;370:937-48.

20. Cumulative Incidence of Death or Myocardial Infarction Stettler C., et al., Lancet 2007;370:937-48.

21. Cumulative Incidence of ARC Definite Stent Thrombosis Stettler C., et al., Lancet 2007;370:937-48.

22. Definite ARC Stent Thrombosis PES vs. BMS HR 95% CI p SES vs. BMS HR 95% CI p SES vs. PES HR 95% CI p Stettler C., et al., Lancet 2007;370:937-48. 1.43 1.14 1.14 1.02 1.00 0.10 0.43 0.04 0.90 0.21 (0.09-1.32) (0.26-1.64) (0.26-0.98) (0.46-3.17) (0.48-1.13) 0.39 0.68 0.54 1.05 0.71 0.64 0.78 0.71 0.96 1.00 (0.27-6.24) (0.45-2.88) (0.62-2.26) (0.46-2.67) (0.68-1.63) 0.07 0.23 0.02 0.90 0.14 (0.86-16.85) (0.65-4.04) (1.19-4.23) (0.38-2.53) (0.96-2.24) 3.57 1.61 2.11 0.95 1.38 >1 - 4 Years BMS PES SES n = 8 n = 26 n = 14 >30 Days – 1 Year BMS PES SES n = 14 n = 16 n = 16 >30 Days – 4 Years BMS PES SES n = 22 n = 42 n = 30 0 – 30 Days BMS PES SES n = 28 n = 30 n = 36 0 Days- 4 Years BMS PES SES n = 50 n = 72 n = 66

23. Protocol Stent Thrombosis PES vs. BMS HR 95% CI p SES vs. BMS HR 95% CI p SES vs. PES HR 95% CI p Stettler C., et al., Lancet 2007;370:937-48. 5.82 0.92 1.13 0.86 1.03 0.046 0.32 0.01 0.63 0.08 (0.05-0.98) (0.32-1.35) (0.25-0.79) (0.42-1.89) (0.41-1.06) 0.30 0.74 0.45 0.84 0.65 0.07 0.80 0.57 0.59 0.92 (0.88-76.89) (0.37-1.69) (0.66-2.81) (0.47-1.70) (0.59-1.67) 0.001 0.62 0.01 0.98 0.13 (3.92-221.7) (0.66-3.07) (1.23-7.00) (0.48-2.07) (0.84-2.58) 20.0 1.32 2.36 1.01 1.56 >1 - 4 Years BMS PES SES n = 2 n = 27 n = 12 >30 Days – 1 Year BMS PES SES n = 20 n = 20 n = 23 >30 Days – 4 Years BMS PES SES n = 22 n = 47 n = 35 0 – 30 Days BMS PES SES n = 35 n = 35 n = 38 0 Days- 4 Years BMS PES SES n = 57 n = 96 n = 85

24. Cumulative Incidence of Death Overall: DM vs. Non-DM Diabetics Non-Diabetics Stettler C., et al., Lancet 2007;370:937-48.

25. Cumulative Incidence of Overall Death or MI: DM vs. Non-DM Diabetics Non-Diabetics Stettler C., et al., Lancet 2007;370:937-48.

26. BMS Strut-Thickness * ISAR-STEREO: RCT enrolling 628 patients with CAD in > 2.8 mm native vessels comparing thin (50  m ACS RX Multi-Link) vs. thick (140  m; Bx Velocity) strut stents: - Angiographic Restenosis at 6 months: 15.0% vs. 25.8%; P=0.003 - Clinical restenosis at 1 year: 8.6% vs. 13.8%; P=0.03 Kastrati A., et al., Circulation 2001;103;2816-2821 This concept is still a debated issue since several analyses of BMS studies have found that strut thickness is not a predictor of TLR: www.TCTMD.com Cutlip D., Strut Thickness: Strut Thickness Has a Minor Impact on Restenosis-Most Bare Metal Stents Are More Alike Than Different!; Monday, December 08, 2003).

28. Influence of Strut Thickness: Death or MI Stettler C., et al., Lancet 2007;370:937-48. SES vs. PES (Adjusted for strut thickness): 0.85 (0.78-0.99)

30. Summary of Key Network Analysis Findings Stettler C., et al., Lancet 2007;370:937-48. 0.70 (0.56-0.84) p = 0.0021 0.30 (0.24-0.37) p < 0.0001 0.42 (0.33-0.53) p<0.0001 TLR Protocol-Defined ST ARC-Definite ST 0.65 (0.41-1.06) p = 0.08 1.03 (0.59-1.67) p = 0.92 1.56 (0.84-2.58) p = 0.13 Overall (0 days-4yrs) 0.71 (0.48-1.13) p = 0.21 1.00 (0.68-1.63) p = 1.00 1.38 (0.96-2.24) p = 0.14 Overall (0 days-4yrs) 0.30 (0.05-0.98) p = 0.046 5.82 (0.88-76.89) p = 0.07 20.02 (3.92-221.7) p = 0.001 Very Late (>1yr-4yrs) 0.74 (0.32-1.35) p = 0.32 0.92 (0.37-1.69) p = 0.80 1.32 (0.66-3.07) p = 0.62 Late (>30 days-1yr) 0.68 (0.26-1.64) p = 0.43 1.14 (0.45-2.88) p = 0.78 1.61 (0.65-4.04) p = 0.23 Late (>30 days-1yr) 0.39 (0.09-1.32) p = 0.10 1.43 (0.27-6.24) p = 0.64 3.57 (0.86-16.85) p = 0.071 Very Late (>1yr-4yrs) 0.83 (0.71-1.00) p = 0.045 0.81 (0.66-0.97) p = 0.030 1.00 (0.81-1.23) p = 0.99 MI 0.96 (0.83-1.24) p = 0.80 1.00 (0.82-1.25) p = 0.89 1.03 (0.84-1.22) p = 0.75 Death SES vs. PES HR (95% CI) SES vs. BMS HR (95% CI) PES vs. BMS HR (95% CI)